Spontaneous evolution of human skin fibroblasts into wound-healing keratinocyte-like cells.

Abstract:

:Producing keratinocyte cells (KCs) in large scale is difficult due to their slow proliferation, disabling their use as seed cells for skin regeneration and wound healing. Cell reprogramming is a promising inducer-based approach to KC production but only reaches very low cellular conversion. Here we reported a unique cellular conversion phenomenon, where human skin fibroblasts (FBs) were spontaneously converted into keratinocyte-like cells (KLCs) over the time without using any inducers. Methods: FBs were routinely cultured for more than 120 days in regular culture medium. Characteristics of KLCs were checked at the molecular and cellular level. Then the functionality and safety of the KLCs were verified by wound healing and tumorigenicity assay, respectively. To identify the mechanism of the cell conversion phenomenon, high-throughput RNA sequencing was also performed. Results: The global conversion started on day 90 and reached 90% on day 110. The KLCs were as functional and effective as KCs in wound healing without causing oncogenicity. The conversion was regulated via a PI3K-AKT signaling pathway mediated by a long non-coding RNA, LINC00672. Modulating the pathway could shorten the conversion time to 14 days. Conclusion: The discovered FBs-KLCs conversion in the study might open a new avenue to the scalable production of cell sources needed for regenerating skins and healing large-area wounds.

journal_name

Theranostics

journal_title

Theranostics

authors

Zhang F,Zhang D,Cheng K,Zhou Z,Liu S,Chen L,Hu Y,Mao C,Liu S

doi

10.7150/thno.31526

subject

Has Abstract

pub_date

2019-07-09 00:00:00

pages

5200-5213

issue

18

issn

1838-7640

pii

thnov09p5200

journal_volume

9

pub_type

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